Ph.D. (Zoology) / Please refer to full text to view abstract

D.Com. (Business Economics) / Please refer to full text to view abstract

This pharmaceutical industry faces many challenges and a decision made one way or the other could pave the way for spectacular success or failure. Over the last ten years, the South Africa (SA) government has actively promoted research and development in human health and local diseases through an extensive series of funding and investment programmes. Unfortunately, to date the strategy has not yielded the results hoped for. An exploratory, in-depth interview based study was conducted in order to inform the feasibility of using a focussed cluster strategy that directs investment on only the most critical of national health priorities that have an effective market and potential for global export growth. There were two main areas identified as potential for a cluster strategy fulfilling the requirements listed which have informed the recommendations for collaboration and partnering in the form of a programme exhibiting an appreciation for the tension and ambiguity that exists between the goals for social good and the economic motive of the private sector creating a shared benefits. Copyright / Dissertation (MBA)--University of Pretoria, 2010. / Gordon Institute of Business Science (GIBS) / unrestricted

The adult ecophenotype of an animal is the result of interactive events which occur during its early ontogeny through a series of sequential steps of increasing morphological complexity. At the step boundaries, there are qualitative and quantitative changes in the structures present which will allow the developing animal to successfully cope with new trophic features of its internal and external environment. There is some controversy as to whether the shifts that occur at these step boundaries are gradual or saltatory. Environmental parameters, early life-history plasticity and genetic instructions are the interactive events which produce the ecophenotype. The early ontogeny of Oreochromis mossambicus was followed from the time of egg activation until juvenilization. The eggs, embryos and larvae were artificially incubated at 25±0.5ºC. The descriptive text and the figures are composites derived from drawings, photomicrographs and observational notes of live and preserved individuals. It was found that the early ontogeny of O. mossambicus consists of an embryonic period of approximately 11 days and a truncated larval period of about 4-5 days. The embryonic period can be further divided into a cleavage, an embryonic and a free-embryonic phase. Comparisons of the early development of three other mouthbrooding and one substrate-spawning cichlid done by other researchers, revealed that the early ontogeny of O. mossambicus closely resembles that of Sarotherodon melanotheron (also a mouthbrooding species). Embryo length and yolksac area changed gradually in the cleavage and embryonic phases, showed little or no change in the free-embryonic phase, and changed rapidly in the larval period. Heart rate increased gradually in the embryonic phase and peaked just before the shift into the free-embryonic phase. Gradual decrease in heart rate occurred in the free-embryonic phase followed by a second peak at the boundary between the embryonic and larval periods. In the larval period, heart rate levelled off. Although distinctive boundaries were not clearly evident at all steps, it was concluded that there are three definite ontogenetic steps which occur at the boundaries between the embryonic phase, the free-embryonic phase and the larval period. These thresholds occur at a point where shifts in the trophic features of the external environment are expected. Regression analysis revealed that two regimes exist for changes in embryo length and yolksac area and that a breakpoint occurs just prior to the boundary between the embryonic and larval periods. It appears that ontogeny is saltatory at points where a change in the trophic features of the environment requires a new set of interactions to occur between the environment and the ecomorphological and eco-ethological features of the animal.

The work described in the thesis seeks to lay a foundation for a better understanding of the use of electrospun nanofibers as a sorbent material. Three miniaturised electrospun nanofiber based solid phase extraction devices were fabricated. For the first two, 10 mg of electrospun polystyrene fibers were used as a sorbent bed for a micro column SPE device (8 mm bed height in a 200 μl pipette tip) and a disk (I) SPE device (5 mm 1 mm sorbent bed in a 1000 μl SPE barrel). While for the third, 4.6 mg of electrospun nylon nanofibers were used as a sorbent bed for a disk (II) SPE device, (sorbent bed consisting of 5 5 mm 350 μm stacked disks in a 500 μl SPE barrel). Corticosteroids were employed as model analytes for performance evaluation of the fabricated SPE devices. Quantitative recoveries (45.5-124.29 percent) were achieved for all SPE devices at a loading volume of 100 μl and analyte concentration of 500 ng ml-1. Three mathematical models; the Boltzmann, Weibull five parameter and the Sigmoid three parameter were employed to describe the break through profiles of each of the sorbent beds. The micro column SPE device exhibited a breakthrough volume of 1400 μl, and theoretical plates (7.98-9.1) while disk (I) SPE device exhibited 400-500 μl and 1.39-2.82 respectively. Disk (II) SPE device exhibited a breakthrough volume of 200 μl and theoretical plates 0.38-1.15. It was proposed that the formats of future electrospun nanofiber sorbent based SPE devices will be guided by mechanical strength of the polymer. The study classified electrospun polymer fibers into two as polystyrene type (relatively low mechanical strength) and nylon type (relatively high mechanical strength).

Antidepressants are widely used in the treatment of depressive illnesses associated with neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. Neuroprotection in such disorders is of vital importance in order to delay the progression of the primary disorder. The pathology of neurodegeneration is not fully understood. It is however widely accepted that oxidative stress and excitotoxicity play a major role. Brain tissue is rich in phospholipids, which are especially prone to oxidation due to the high level of oxygen utilization in the brain. In addition, the brain lacks defence mechanisms to protect it against the wrath of free radicals. Presently, there is a wide variety of antidepressant drugs available. These range from the original tricyclic antidepressants to the newer selective serotonin reuptake inhibitors. It is not known whether antidepressant drugs, old or new, offer neuroprotection or how the existing state and/or the progression of neurodegeneration, is influenced by these agents. The present study was undertaken to determine how nortriptyline, trimipramine and fluoxetine affect neurodegeneration. Initial in vitro and in vivo studies show that all three of the antidepressants (0-1mM) studied provide neuroprotection from quinolinic acid induced lipid peroxidation. A histological investigation supported these findings by showing that a marginal degree of neuroprotection is apparent when treating animals with antidepressants (10mg/kg) before and following quinolinic acid intrastriatal injection. Further studies were undertaken in an attempt to determine the mode of neuroprotective action of the agents studied. An in vitro study of superoxide anion induced lipid peroxidation indicates that these agents do not act as antioxidants. The influence of the antidepressants on tryptophan 2,3-dioxygenase activity was assessed, based on the understanding that inhibition of this enzyme results in increased levels of the known antioxidant indoleamine, melatonin. Nortriptyline hydrochloride is seen to inhibit tryptophan 2,3-dioxygenase activity and as such it is possible that this antidepressant can indirectly provide neuroprotection by increasing available melatonin. Electrochemical and UV/visible studies show that trimipramine maleate interacts with free iron (II) and iron (III) ions. Free metal ions can catalyse the formation of damaging free radicals. Through interaction with trimipramine maleate, these ions will be unavailable to the system and thus cannot contribute to oxidative stress. The findings of this study indicate that antidepressants may be able to provide neuroprotection to neuronal cells. The mode of such neuroprotective actions need to be further examined so that patients suffering from depression coexisting with neurodegenerative diseases can be safely and effectively treated.

The work presented in this thesis forms part of a continuing programme concerned with the structural determination of capsular polysaccharides of some Enterobacteriaceae. Since bacteria of this family are pathogenic to Man, work in this laboratory has focused on the structural elucidation of Klebsiella and, more recently, Escherichia coli ( E. coli) capsular polysaccharides ( K-antigens ). To date, some 74 K-antigens have been distinguished serologically within the genus E. coli and the structures of approximately 70% are known. In general, the K-antigens of the E. coli are characterized by a wide variety of constituent monosaccharides arranged in repeating units. In this thesis the structural elucidation of the capsular polysaccharides of E. coli serotypes 08: KI02: H- and 08: K47: H2 is presented. A variety of chemical techniques has been employed in the structural analysis, and are discussed. The thesis also includes extensive two-dimensional n.m.r. studies on the E. coli KI02 and K47 polysaccharides, as well as on a modified KI02 polymer produced after a lithium-ethylenediamine degradation of the native polysaccharide.

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Technical advances in the past decade have enabled the development of very fast but expensive component placement machines for the production of Printed Circuit Boards (PCBs). However, when these fast machines have to assemble small volumes of many different types of circuit boards, the machine set-up time becomes much more important than the assembly rate of each board. In order to minimize this set up time, we must try to solve the set-up/sequencing decision problem according to either the MCS (Minimizing Component Switches) or MSI (Minimizing Switching Instants) performance criterion, or both. We examine the set-up/sequencing decision problem for a single machine (work cell) which has high mix low volume production schedules. We compare and improve methods which attempt to solve this problem, and we develop our own heuristics for solving this problem when both performance criteria are of great importance. We use lower bounds to determine how good our results are, and we discuss how to adapt methods which we have looked at to different manufacturing environments.